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The present invention relates generally to a method and system for use in treating a patient with a biological substance to optimize therapy and to prevent an adverse response. More particularly, the present invention relates to a method and system for use in treating a patient with vaccines, serums, and/or drugs. The present invention can utilize either biological substance levels or other surrogate markers to determine the effectiveness of the dosing regimen and, if necessary, to suggest a new more optimal biological substance dose.
The term xe2x80x9cbiological substancexe2x80x9d as used herein means all biological substances and includes, but is not limited to, vaccines, serums, drugs, adjuvants to enhance or modulate a resulting immune response, vitamin antagonists, medications, and all substances derived from and/or related to the foregoing substances.
Furthermore, wherever the generic term xe2x80x9cbiological substancexe2x80x9d is used herein it is also intended to mean species which employ any or more of the individual biological substances as defined and/or alluded to herein.
The term xe2x80x9cvaccinexe2x80x9d or xe2x80x9cvaccinesxe2x80x9d as used herein means all vaccines and includes, but is not limited to: autologous whole-cell vaccines (using cells derived from a patient""s own tumor); allogenic whole-cell vaccines (using cancer cell lines established in vitro and then used to vaccinate multiple patients); tumor specific antigen/tumor associated antigen (TSA/TAA) based vaccines and hormonal autoimmunization approaches; all other cancer vaccines; Melacine; CancerVax; immune-boosting interferon; peptides; dendritic cells having melanoma protein thereon; interleukin-12; substances which stimulate or energize blood cells known as CD8 T cells; genes which make interleukin-12; tumor cells weakened by genes which make interleukin-12; substances which block blood-vessel formation to prevent growth of tumors; immunized cells; recombinant subunit vaccines; DNA vaccines; live recombinant viral vector vaccines; live recombinant bacterial vector vaccines; live-attenuated vaccines; whole-inactivated vaccines; virus-like particle vaccines; synthetic peptide vaccines; xe2x80x9cJennerianxe2x80x9d vaccines; complex vaccines; and combinations of two or more of the foregoing.
The term xe2x80x9csurrogate markerxe2x80x9d as used herein means all surrogate markers and includes, but is not limited to: a measurement of biological activity within the body which indirectly indicates the effect of treatment on a disease state or on any condition being treated; and any measurement taken on a patient which relates to the patient""s response to an intervention, such as the intervention of a biological substance introduced into or on the patient. For example, CD4 cell counts and viral load are examples of surrogate markers in HIV infection.
When a patient begins taking a biological substance or any medication for a length of time, a titration of the amount of biological substance taken by the patient is necessary in order to achieve the optimal benefit of the biological substance, and at the same time to prevent any undesirable side effects that taking too much of the biological substance could produce. Thus, there is a continuous balance between taking enough of the biological substance in order to gain the benefits from that biological substance, and at the same time not taking so much biological substance as to illicit a toxic event.
There is large inter-individual variability in the patient biological interactions and/or the patient pharmocodynamic and pharmacokinetic interactions of biological substances. What may be an appropriate biological substance dose for one individual, may be too much or too little for another. A physician was required to estimate the correct biological substance dosage for a patient and then to experiment with that dosage, usually by trial and error, until the correct dosage was achieved. Likewise, the FDA labeling of a biological substance suggests dosages based on epidemiological studies and again does not account for inter-individual variability. Non-linear least squares modeling methods involve the use of large amounts of data relating to a general population in order to calculate a best fit. Much like linear regression models, this method cannot take into account the variability between people with the same population characteristics.
Bayesian analysis is another method used to relate biological substance dose to efficacy. This method employs large-scale population parameters to stratify a population in order to better characterize the individuals. This method does not take into account the changes that can occur within a person over time, and as a result cannot reliably estimate dosages.
Pharmacokinetic compartment modeling has had success with some biological substances, but because the models are static and cannot adapt themselves to changes within a population or a patient, they are once again undesirable for dynamically determining biological substance dosages.
Expert systems have been developed using similar technology to predict specific drug dosages for specific immunosuppressant drugs (see, e.g., U.S. Pat. Nos. 5,365,948, 5,542,436 and 5,694,950). These algorithms, however, are not generic and only use immunosuppressant blood levels. Each algorithm is specific to an individual specific immunosuppressant drug. As it stands, these inventions cannot be applied to other biological substances and do not have a non-linear feedback loop mechanism.
The present invention provides in one embodiment thereof a method for calculating a revised dose of a biological substance for a patient using said biological substance, comprising the steps of: accepting as a first input the patient""s current biological substance dose; accepting as a second input a maximum dose of said biological substance; accepting as a third input a percent response of the patient based on one or more surrogate markers for said patient; and determining a revised dose, wherein said revised dose is a function of said current dose minus a ratio of the percent response of the patient and a ratio of said current dose to said maximum dose plus the percent of individual patient response multiplied by a response factor.
The present invention provides in another embodiment thereof a method for calculating a revised dose of a biological substance for a patient using said biological substance comprising the steps of: accepting as a first input the patient""s current biological substance dose; accepting as a second input the maximum dose of the biological substance; accepting as a third input one or more numerical markers indicating a response of the patient; and calculating said revised dose, wherein said revised dose is a function of said current dose minus the ratio of the change in numerical markers and the ratio of said current dose to said maximum dose plus the percent of individual patient response multiplied by a response factor. According to the present invention, patient dosing occurs through a cyclic series of events, depicted in flow chart form in FIG. 1. After an initial examination, an initial dose of a biological substance, such as a cancer vaccine, is prescribed and administered by a physician for a patient. The initial dose is based on the FDA recommended dosage found on the biological substance label. The biological substance dose is further refined upon repeated dosing by the physician based on the patient""s response to the biological substance. Too much biological substance could cause the patient to experience toxic biological substance effects, and the biological substance dose would need to be reduced. Too little biological substance could cause the patient not to receive the benefit the biological substance therapy could offer, and the dosage would need to be increased.
A preferred embodiment of the invention requires that a physician determine the percentage of response by the patient to the biological substance based on the surrogate markers for that biological substance. A relationship is then employed which uses the input parameters described above to determine the next dose for the patient.
Each specie of the invention has two preferred embodiments; one which uses actual numerical surrogate markers to calculate a dose, and another embodiment that uses percentages as the numerical input for the surrogate markers.